Herpes simplex virus (HSV) infections are widespread in human populations, and pose a particularly difficult health problem. There is currently no cure for herpes infections. Many of the drugs currently in clinical use may not be effective in reducing the severity or duration of the systems. Even after the symptoms disappear, herpes virus tends to remain dormant in nerve tissue, only to be reactivated at a later date to an active phase of infection, causing lesions ("cold sores") and other symptoms to recur. A drug can be considered effective if it diminishes the severity of the lesions, allows for more rapid healing, extends the period between recurrences of herpes infections or stops recurrences altogther.
Herpes simplex virus is one member of the family "Herpetoviridae"; other members of this family which infect humans are varicella-zoster, cytomegalovirus and Epstein-Barr virus. The family also includes various members which attack animals. For example, there are three types of equine herpesvirus, a swine herpesvirus, a canine herpesvirus and a feline herpesvirus, among others.
As with all viruses, herpes virus invades healthy host cells on which it relies to provide its needs for replication. Herpes viruses code for some of the enzymes they need for replication, instead of relying completely on the host cell for all their needs. Hence, herpes viruses are subject to selective inhibition by certain drugs that interfere specifically with viral enzymes. A variety of drugs have been proposed and tested for treatment of HSV infections. For example, U.S. Pat. No. 4,199,574 Schaeffer, issued Apr. 22, 1980 discloses a wide variety of compounds said to be useful in such treatments, extensive testing of one of which (acycloguanosine or acyclovir, 9-[2-hydroxyethoxymethyl]guanine) has been reported in the literature, with sometimes promising results. Another drug which has been explored is 5-iododeoxyuridine (IDU), but this has been reported to be effective only against herpes infections of the eyes. It also has undesirable side effects, associated with toxicity to normal cells. Adenine arabinoside (ara-A), phosphonoformic acid (PFA), phosphonoacetic acid (PAA), 2-deoxy-D-glucose (2DG), and 5-(2-halogenovinyl)-2'-deoxyuridines as exemplified by bromovinyl-deoxyuridine (BVDU) and its iodo-analog are other drugs which have some demonstrated activity against human herpesviruses.
U.S. Pat. No. 3,767,795 Schleicher et al, assigned to Abbott Laboratories, describes a method of preventing or treating herpesvirus infections in animals by administering phosphonoacetic acid or its salts.
U.S. Pat. No. 4,215,113 Eriksson et al, assigned to Astra Lakemedel AB, describes a method of treating virus infections, including herpesvirus, by administering phosphonoformic acid or its salts to infected animals.
U.S. Pat. No. 4,347,360 Ogilvie, discloses compounds such as 9-[[2-hydroxy-1-(hydroxymethyl)-ethoxy]-methyl] adenine and analogues thereof as active against herpes simplex virus.
U.S. Pat. No. 4,355,032 Verheyden et al and U.S. patent application Ser. No. 301,790 Ogilvie both teach that 9-[[2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl] guanine (also known as 9-(1,3-dihydroxy-2-propoxymethyl)-guanine) is active against herpes simplex virus.
Patent Co-operation Treaty Application US82/00/182 K. O. Smith and ens BIO LOGICALS inc., describes synergistic mixtures of 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl] guanine and PFA or PAA or salts thereof, for use in treatment of herpes virus infected cells.